Paul L. Hess

Implantable Cardioverter-Defibrillators for Primary Prevention of Sudden Cardiac Death in CKD: A Meta-analysis of Patient-Level Data From 3 Randomized Trials

BACKGROUND The benefit of a primary prevention implantable cardioverter-defibrillator (ICD) among patients with chronic kidney disease is uncertain. STUDY DESIGN Meta-analysis of patient-level data from randomized controlled trials. SETTING & POPULATION Patients with symptomatic heart failure and left ventricular ejection fraction<35%. SELECTION CRITERIA FOR STUDIES From 7 available randomized controlled studies with patient-level data, we selected studies with available data for important covariates. Studies without patient-level data for baseline estimated glomerular filtration rate (eGFR) were excluded. INTERVENTION Primary prevention ICD versus usual care effect modification by eGFR. OUTCOMES Mortality, rehospitalizations, and effect modification by eGFR. RESULTS We included data from the Multicenter Automatic Defibrillator Implantation Trial I (MADIT-I), MADIT-II, and the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT). 2,867 patients were included; 36.3% had eGFR<60 mL/min/1.73m2. Kaplan-Meier estimate of the probability of death during follow-up was 43.3% for 1,334 patients receiving usual care and 35.8% for 1,533 ICD recipients. After adjustment for baseline differences, there was evidence that the survival benefit of ICDs in comparison to usual care depends on eGFR (posterior probability for null interaction P<0.001). The ICD was associated with survival benefit for patients with eGFR≥60 mL/min/1.73 m2 (adjusted HR, 0.49; 95% posterior credible interval, 0.24-0.95), but not for patients with eGFR<60 mL/min/1.73 m2 (adjusted HR, 0.80; 95% posterior credible interval, 0.40-1.53). eGFR did not modify the association between the ICD and rehospitalizations. LIMITATIONS Few patients with eGFR<30 mL/min/1.73 m2 were available. Differences in trial-to-trial measurement techniques may lead to residual confounding. CONCLUSIONS Reductions in baseline eGFR decrease the survival benefit associated with the ICD. These findings should be confirmed by additional studies specifically targeting patients with varying eGFRs.

Survival Benefit of the Primary Prevention Implantable Cardioverter-Defibrillator Among Older Patients Does Age Matter? An Analysis of Pooled Data From 5 Clinical Trials

Background—The impact of patient age on the risks of death or rehospitalization after primary prevention implantable cardioverter-defibrillator (ICD) placement is uncertain. Methods and Results—Data from 5 major ICD trials were merged: the Multicenter Automatic Defibrillator Implantation Trial I (MADIT-I), the Multicenter UnSustained Tachycardia Trial (MUSTT), the Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II), the Defibrillators in Nonischemic Cardiomyopathy Treatment Evaluation Trial (DEFINITE), and the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT). Median age at enrollment was 62 (interquartile range 53–70) years. Compared with their younger counterparts, older patients had a greater burden of comorbid illness. In unadjusted exploratory analyses, ICD recipients were less likely to die than nonrecipients in all age groups: among patients aged <55 years: hazard ratio 0.48, 95% posterior credible interval 0.33 to 0.69; among patients aged 55 to 64 years: hazard ratio 0.69, 95% posterior credible interval 0.53 to 0.90; among patients aged 65 to 74 years: hazard ratio 0.67, 95% posterior credible interval, 0.53 to 0.85; and among patients aged ≥75 years: hazard ratio 0.54, 95% posterior credible interval 0.37 to 0.78. Sample sizes were limited among patients aged ≥75 years. In adjusted Bayesian–Weibull modeling, point estimates indicate ICD efficacy persists but is attenuated with increasing age. There was evidence of an interaction between age and ICD treatment on survival (two-sided posterior tail probability of no interaction <0.01). Using an adjusted Bayesian logistic regression model, there was no evidence of an interaction between age and ICD treatment on rehospitalization (two-sided posterior tail probability of no interaction 0.44). Conclusions—In this analysis, the survival benefit of the ICD exists but is attenuated with increasing age. The latter finding may be because of the higher burden of comorbid illness, competing causes of death, or limited sample size of older patients. There was no evidence that age modifies the association between ICD treatment and rehospitalization.

Chronic pacing and adverse outcomes after transcatheter aortic valve implantation

Objective Many patients undergoing transcatheter aortic valve implantation (TAVI) have a pre-existing, permanent pacemaker (PPM) or receive one as a consequence of the procedure. We hypothesised that chronic pacing may have adverse effects on TAVI outcomes. Methods and results Four groups of patients undergoing TAVI in the Placement of Aortic Transcatheter Valves (PARTNER) trial and registries were compared: prior PPM (n=586), new PPM (n=173), no PPM (n=1612), and left bundle branch block (LBBB)/no PPM (n=160). At 1 year, prior PPM, new PPM and LBBB/no PPM had higher all-cause mortality than no PPM (27.4%, 26.3%, 27.7% and 20.0%, p<0.05), and prior PPM or new PPM had higher rehospitalisation or mortality/rehospitalisation (p<0.04). By Cox regression analysis, new PPM (HR 1.38, 1.00 to 1.89, p=0.05) and prior PPM (HR 1.31, 1.08 to 1.60, p=0.006) were independently associated with 1-year mortality. Surviving prior PPM, new PPM and LBBB/no PPM patients had lower LVEF at 1 year relative to no PPM (50.5%, 55.4%, 48.9% and 57.6%, p<0.01). Prior PPM had worsened recovery of LVEF after TAVI (Δ=10.0 prior vs 19.7% no PPM for baseline LVEF <35%, p<0.0001; Δ=4.1 prior vs 7.4% no PPM for baseline LVEF 35–50%, p=0.006). Paced ECGs displayed a high prevalence of RV pacing (>88%). Conclusions In the PARTNER trial, prior PPM, along with new PPM and chronic LBBB patients, had worsened clinical and echocardiographic outcomes relative to no PPM patients, and the presence of a PPM was independently associated with 1-year mortality. Ventricular dyssynchrony due to chronic RV pacing may be mechanistically responsible for these findings. Trial registration number (ClinicalTrials.gov NCT00530894).

Survival After Primary Prevention Implantable Cardioverter-Defibrillator Placement Among Patients With Chronic Kidney Disease

Background—Guidelines recommend that implantable cardioverter-defibrillator (ICD) candidates have an estimated longevity of ≥1 year. Longevity can be affected by chronic kidney disease (CKD). Methods and Results—Using the National Cardiovascular Data Registry ICD registry linked with the Social Security Death Master File, we assessed the rate of death after primary prevention ICD placement between January 1, 2006, and December 31, 2007, according to CKD stage. Using Cox models, we identified factors associated with death among patients with CKD. Compared with patients without CKD (n=26 056), those with CKD (n=21 226) were older, less commonly men, more often white, and more frequently had comorbid illness. Compared with patients without CKD, patients with a glomerular filtration rate 30 to 60, glomerular filtration rate <30, and end-stage renal disease on dialysis had a higher risk of death after ICD placement (hazard ratio, 2.08; 95% confidence interval, 1.99–2.18; P<0.0001; hazard ratio, 4.20; 95% confidence interval, 3.92–4.50; P<0.0001; and hazard ratio, 4.80; 95% confidence interval, 4.46–5.17; P<0.0001, respectively). Corresponding 1-year death rates were 4.4%, 9.1%, 20.2%, and 22.4%. Among patients with CKD, factors associated with increased risk of death included CKD severity, age >65 years, heart failure symptoms, diabetes mellitus, lung disease, serum sodium <140 mEq/L, atrial fibrillation or flutter, and a lower ejection fraction. Conclusions—The risk of death after primary prevention ICD placement is proportional to CKD severity. Among patients with CKD, several factors are prognostically significant and could inform clinical decision making on primary prevention ICD candidacy.

Addressing barriers to optimal oral anticoagulation use and persistence among patients with atrial fibrillation: Proceedings, Washington, DC, December 3-4, 2012

Approximately half of patients with atrial fibrillation and with risk factors for stroke are not treated with oral anticoagulation (OAC), whether it be with vitamin K antagonists (VKAs) or novel OACs (NOACs); and of those treated, many discontinue treatment. Leaders from academia, government, industry, and professional societies convened in Washington, DC, on December 3-4, 2012, to identify barriers to optimal OAC use and adherence and to generate potential solutions. Participants identified a broad range of barriers, including knowledge gaps about stroke risk and the relative risks and benefits of anticoagulant therapies; lack of awareness regarding the potential use of NOAC agents for VKA-unsuitable patients; lack of recognition of expanded eligibility for OAC; lack of availability of reversal agents and the difficulty of anticoagulant effect monitoring for the NOACs; concerns with the bleeding risk of anticoagulant therapy, especially with the NOACs and particularly in the setting of dual antiplatelet therapy; suboptimal time in therapeutic range for VKA; and costs and insurance coverage. Proposed solutions were to define reasons for oral anticoagulant underuse classified in ways that can guide intervention and improve use, to increase awareness of stroke risk as well as the benefits and risks of OAC use via educational initiatives and feedback mechanisms, to better define the role of VKA in the current therapeutic era including eligibility and ineligibility for different anticoagulant therapies, to identify NOAC reversal agents and monitoring strategies and make knowledge regarding their use publicly available, to minimize the duration of dual antiplatelet therapy and concomitant OAC where possible, to improve time in therapeutic range for VKA, to leverage observational data sets to refine understanding of OAC use and outcomes in general practice, and to better align health system incentives.

Follow-up of patients with new cardiovascular implantable electronic devices: are experts' recommendations implemented in routine clinical practice?

Background— A 2008 expert consensus statement outlined the minimum frequency of follow-up of patients with cardiovascular implantable electronic devices (CIEDs). Methods and Results— We studied 38 055 Medicare beneficiaries who received a new CIED between January 1, 2005, and June 30, 2009. The main outcome measure was variation of follow-up by patient factors and year of device implantation. We determined the number of patients who were eligible for and attended an in-person CIED follow-up visit within 2 to 12 weeks, 0 to 16 weeks, and 1 year after implantation. Among eligible patients, 42.4% had an initial in-person visit within 2 to 12 weeks. This visit was significantly more common among white patients than black patients and patients of other races (43.0% versus 36.8% versus 40.5%; P <0.001). Follow-up within 2 to 12 weeks improved from 40.3% in 2005 to 55.1% in 2009 ( P <0.001 for trend). The rate of follow-up within 0 to 16 weeks was 65.1% and improved considerably from 2005 to 2009 (62.3%–79.6%; P <0.001 for trend). Within 1 year, 78.0% of the overall population had at least 1 in-person CIED follow-up visit. Conclusions— Although most Medicare beneficiaries who received a new CIED between 2005 and 2009 did not have an initial in-person CIED follow-up visit within 2 to 12 weeks after device implantation, the rate of initial follow-up improved appreciably over time. This CIED follow-up visit was significantly more common in white patients than in patients of other races.Background—A 2008 expert consensus statement outlined the minimum frequency of follow-up of patients with cardiovascular implantable electronic devices (CIEDs). Methods and Results—We studied 38 055 Medicare beneficiaries who received a new CIED between January 1, 2005, and June 30, 2009. The main outcome measure was variation of follow-up by patient factors and year of device implantation. We determined the number of patients who were eligible for and attended an in-person CIED follow-up visit within 2 to 12 weeks, 0 to 16 weeks, and 1 year after implantation. Among eligible patients, 42.4% had an initial in-person visit within 2 to 12 weeks. This visit was significantly more common among white patients than black patients and patients of other races (43.0% versus 36.8% versus 40.5%; P<0.001). Follow-up within 2 to 12 weeks improved from 40.3% in 2005 to 55.1% in 2009 (P<0.001 for trend). The rate of follow-up within 0 to 16 weeks was 65.1% and improved considerably from 2005 to 2009 (62.3%–79.6%; P<0.001 for trend). Within 1 year, 78.0% of the overall population had at least 1 in-person CIED follow-up visit. Conclusions—Although most Medicare beneficiaries who received a new CIED between 2005 and 2009 did not have an initial in-person CIED follow-up visit within 2 to 12 weeks after device implantation, the rate of initial follow-up improved appreciably over time. This CIED follow-up visit was significantly more common in white patients than in patients of other races.

Contemporary Management of Atrial Fibrillation: What Can Clinical Registries Tell Us About Stroke Prevention and Current Therapeutic Approaches?

Atrial fibrillation (AF) is a global health problem. The condition brings an increased risk of stroke, systemic embolism, and heart failure (HF) and is associated with impaired quality of life, frequent hospitalizations, and mortality.[1][1] Observational studies have been the main source of

Effect of the 2014 atrial fibrillation guideline revisions on the proportion of patients recommended for oral anticoagulation.

Effect of the 2014 Atrial Fibrillation Guideline Revisions on the Proportion of Patients Recommended for Oral Anticoagulation In 2014, the American Heart Association, American College of Cardiology, and Heart Rhythm Society published a revised guideline for atrial fibrillation (AF) treatment recommending use of a refined stroke risk score and revised threshold for oral anticoagulation (OAC) initiation.1 We assessed the potential effect of this new guideline by comparing the proportion of patients with AF recommended for OAC under the 2011 and 2014 guidelines.1,2

The Role of Cardiovascular Implantable Electronic Devices in the Detection and Treatment of Subclinical Atrial Fibrillation: A Review

Importance Subclinical atrial fibrillation (AF) is associated with an increased risk for stroke. Observations Subclinical AF is asymptomatic, short in duration, and usually detected with long-term, continuous monitoring. Most prior studies have explored its consequences using cardiovascular implantable electronic devices (CIEDs). Although current prevalence estimates are derived from study populations with prior CIEDs, 3 trials will assess the time to a first AF diagnosis among patients receiving a CIED for purposes of AF detection. Stroke risk estimates are currently limited to patients with a prior CIED and vary widely, ranging from a hazard ratio of 0.87 (95% CI, 0.58-1.31) to 9.40 (95% CI, 1.80-47.00). Stroke risk pathogenesis may include factors that are proximately causal, upstream risk activators, and risk markers. The treatment of subclinical AF may be a useful stroke prevention strategy; however, no direct evidence of benefit from oral anticoagulation exists in this population. Two ongoing trials will assess the risk and benefit of non–vitamin K oral anticoagulants among patients at high risk for stroke with a previously placed implantable CIED, but without a prior diagnosis of clinical AF. If clinical benefit is proven, then the cost-effectiveness of screening for and the treatment of subclinical AF will require additional study. Conclusions and Relevance At present, no evidence suggests that implanting a CIED to detect AF or initiating oral anticoagulation therapy among those in whom AF is detected is beneficial. Ongoing and future studies will identify people at high risk for developing subclinical AF and will evaluate the efficacy, safety, and economic value of oral anticoagulation therapy in this population.

Outcomes associated with warfarin use in older patients with heart failure and atrial fibrillation and a cardiovascular implantable electronic device: findings from the ADHERE registry linked to Medicare claims.

Warfarin use and associated outcomes in patients with heart failure and atrial fibrillation and a cardiovascular implantable electronic device have not been described previously.